Background: Anti-CD19 chimeric antigen receptor (CAR) T cells for relapse/refractory B-cell malignancies has been remarkably effective in previous clinical trials. However, most of subjects has severe adverse effect even though the infusion of CAR T cells is at the low dose. Herein, we investigated the safety of administering CAR T cells which express the anti-CD19 chimeric antigen receptor in synthetic biology optimizing system. Methods: We designed an anti-CD19 CAR with FMC63 Scfv (KD-019). This CAR has a CD8 hinge and transmembrane domains and a 4-1BB costimulatory domain; T cells expresses CAR in synthetic biology optimizing system. A phase I dose-escalation trial was conducted to investigate the safety of KD-019 CAR T cells and to assess efficacy for patients with previously treated B-cell lymphoma. The patient at the 76 years old received Flu/Cy chemotherapy to enhance CAR T cells activity. Two days after the completion of chemotherapy, about 3 million KD-019 CAR T cells were infused. Results: The patient who has chemotherapy-refractory lymphoma has received KD-019 CAR T cells infusion. Post infusion KD-019 CAR T cells expansion were observed; peak CAR T cells level occurred between Day 3 and 10, and CAR T cells were still detected on Day 243. In addition, we found that CD3+CD8+ T cells level peaked on Day 15. Moreover, after infusion of CAR-T cells, the right peripheral pulmonary lymphaden and visible nodules were respectively shrunk by 53% and 85% on Day 28; and some peripheral pulmonary nodules were obviously reduced and nearly disappeared. We also found that pelvic effusion was significantly reduced, and pain symptoms of the left hip and leg were reduced by 50%. Exhilaratingly, our KD-019 CAR therapy has no obvious cytokine release syndrome (CRS) and central nervous system toxicity. Conclusions: KD-019 CAR T cells express an anti-CD19 chimeric antigen receptor in synthetic biology optimizing system. this innovative KD-019 product can offer significant clinical benefit for NHL patients at the low dose without fever and neurotoxicity. Clinical trial information: NCT03854994. Clinical trial information: NCT03854994.